This proposal seeks funds to establish a Center for Humanized Mice Development. This new facility at the University of Nebraska Medical Center (UNMC) will offer environmentally, genetically, and xenotransplantation- engineered mouse models for translational studies and drug discovery, which are the mainstream at UNMC. It is well known that often clinical studies are successful in animal models but fail at the human level. Also the focused use of micro-animals, mice in particular, makes applicability to humans problematic. In turn, we are developing a resource that will generate improved animal models to study human immunity, human-specific infections, vaccines, and human-specific drug interactions. The resources are expected to be efficiently utilized for speeding the translation of new therapeutics to patients. Our goals to improve existing strains of mice are as follows: modify mouse backgrounds for the studies of human-like adaptive immune responses to broader range of pathogens and evaluation of vaccine candidates, create strains of mice that are compatible with the function of human immune system based on human-like glycosilation patterns, modify mouse backgrounds for studies of human-like drug metabolism and drug interaction, study HIV-1-related co-infections, such as hepatitis, tuberculosis, and malaria, and lastly examine HIV-1-associated comorbidities, including end-organ diseases like HIV-1-associated neurocognitive disorders (HAND).